From gut inflammation to psychiatric comorbidity: mechanisms and therapies for anxiety and depression in inflammatory bowel disease

Abstract

Abstract Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), is characterized by complex aetiological factors and extensive extraintestinal manifestations. Anxiety and depression, which are common mental disorders, have shown increasing incidence rates in recent years. Compared with the general population, IBD patients are more susceptible to anxiety and depression, which consequently exacerbate the disease burden and increases the risk of adverse clinical outcomes. Emerging evidence reveals shared pathophysiological mechanisms between IBD and anxiety and depression. This review rigorously focuses on anxiety and depression in IBD, distinguishing these conditions from primary anxiety or depressive disorders, as well as from mood disturbances secondary to other chronic illnesses, and summarizes the latest research literature highlighting their unique comorbid characteristics. Firstly, we integrate recent epidemiological evidence to establish their bidirectional relationship. Subsequently, we summarize the comorbid mechanisms as follows: genetic predisposition, impaired hippocampal neurogenesis, specific brain region alterations, gut microbiota dysbiosis, hypothalamic‒pituitary‒adrenal (HPA) axis dysregulation and neuroimmune interactions mediated by inflammatory cytokines and neurotransmitters. Finally, we explore novel therapeutic approaches derived from these mechanistic insights, aiming to enhance clinical recognition of this bidirectional comorbidity and optimize the management of such comorbid conditions.

Keywords

• Depression
• Anxiety
• Inflammatory bowel disease
• Microbiota‒gut‒brain axis
• Neuroimmune
• Pharmacotherapy